Cancer remains the number two cause of mortality in the United States, resulting in over 500,000 deaths per year. Despite advances in detection and treatment, cancer mortality remains high. New compositions and methods for the imaging and treatment (e.g., therapeutic) of cancer may help to reduce the rate of mortality associated with cancer.
Severe, chronic pain is observed on a variety of subjects. For example, there exist large numbers of individuals with severe pain associated with arthritis, autoimmune disease, injury, cancer, and a host of other conditions.
There exists a need for compositions, methods and systems for delivering agents (e.g., diagnostic and/or therapeutic (e.g., cancer therapeutics, pain relief agents) to subjects that provide effective therapy (e.g., disease treatment, symptom relief, etc.) with reduced or eliminated side effects, even when administered in high doses. Functionalized dendrimers, such as PAMAM dendrimers conjugated with functional ligands relevant to cancer therapy and/or pain alleviation, have been developed for such purposes. However, multi-step conjugation strategies used to attach different functional groups to the surfaces of nanoparticles (e.g., dendrimers, PAMAM dendrimer branches) introduce higher polydispersity and require multiple processing steps, thereby complicating synthesis. In addition, increased polydispersity of functionalized dendrimer products can negatively affect properties such as therapeutic potency, pharmacokinetics, or effectiveness for multivalent targeting.
Improved methods of synthesis of dendrimers resulting in decreased polydispersity are needed. In particular, compositions and methods that facilitate copper-free click conjugation for use in the synthesis of functionalized dendrimers are needed.